Personality traits and disorders among adult adhd patients: Do they vary between males and females?

INTRODUCTION: Patients with Attention Deficit/Hyperactivity Disorder (ADHD) have shown an increased risk of developing a DSM Cluster B (i.e., Borderline, OR=13.16; Antisocial, OR=3.03; Narcissistic, OR=8.69) and DSM Avoidant Personality Disorder (PD; OR=9.77; Miller et al., 2008). Although different comorbidities affect males and females with ADHD (Kooij et al., 2013), gender differences in personality traits and disorders have not yet been investigated. OBJECTIVES: To describe gender differences in personality traits and disorders among a sample of adult outpatients with ADHD. METHODS: A consecutive sample of DSM-5 ADHD outpatients was recruited at the Adult ADHD Center of the “San Luigi” University Hospital (Orbassano (TO), Italy) between Jan 2017 and Jan 2018. Patients’ personality was assessed by Millon Clinical Multiaxial Inventory (MCMI-III; Zennaro et al, 2008). RESULTS: The study sample consisted of 82 males and 31 females. Sixty percent of men vs. 77% of women had a personality disorder ( CONCLUSIONS: Women with ADHD showed a higher frequency of personality disorders and higher rate of Masochistic PD than men. Moreover, the two most important clusters detected in women included severe personality components (i.e., Borderline and Paranoid) when compared with men. Further studies on larger samples should be conducted to confirm more severe personality profiles in women than in men. DISCLOSURE: No significant relationships

New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps

Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein

Enzymatically active apurinic/apyrimidinic endodeoxyribonuclease 1 is released by mammalian cells through exosomes

The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1), the main AP-endonuclease of the DNA base excision repair pathway, is a key molecule of interest to researchers due to its unsuspected roles in different nonrepair activities, such as: I) adaptive cell response to genotoxic stress, ii) regulation of gene expression, and iii) processing of microRNAs, which make it an excellent drug target for cancer treatment. We and others recently demonstrated that APE1 can be secreted in the extracellular environment and that serum APE1 may represent a novel prognostic biomarker in hepatocellular and non-smallcell lung cancers. However, the mechanism by which APE1 is released extracellularly was not described before. Here, using three different approaches for exosomes isolation: Commercial kit, nickel-based isolation, and ultracentrifugation methods and various mammalian cell lines, we elucidated the mechanisms responsible for APE1 secretion. We demonstrated that APE1 p37 and p33 forms are actively secreted through extracellular vesicles (EVs), including exosomes from different mammalian cell lines. We then observed that APE1 p33 form is generated by proteasomal-mediated degradation and is enzymatically active in EVs. Finally, we revealed that the p33 form of APE1 accumulates in EVs upon genotoxic treatment by cisplatin and doxorubicin, compounds commonly found in chemotherapy pharmacological treatments. Taken together, these findings provide for the first time evidence that a functional Base Excision Repair protein is delivered through exosomes in response to genotoxic stresses, shedding new light into the complex noncanonical biological functions of APE1 and opening new intriguing perspectives on its role in cancer biology

TCO Optimization in Si Heterojunction Solar Cells on p-type Wafers with n-SiOx Emitter☆

Abstract Silicon heterojunction solar cells have largely demonstrated their suitability to reach high efficiencies. We have here focused on p-type c-Si wafers as absorber, considering that they share more than 90% of the solar cell market. To overcome some of the issues encountered in the conventional (n)a-Si:H/(p)c-Si configuration, we have implemented a mixed phase n-type silicon oxide (n-SiOx) emitter in order to gain from the wider bandgap and lower activation energy of this material with respect to (n)a-Si:H. The workfunction of the transparent conductive oxide layer (WTCO) plays also a key role, as it may induce an unfavourable band bending at the interface with the emitter. We have here focused on AZO, a promising alternative to ITO. Different layers with varying WTCO were prepared, by changing relevant deposition parameters, and were tested into solar cells. The experimental results have been explained with the aid of numerical simulations. Finally, for the n-SiOx/(p)c-Si heterojunction with optimized WTCO a potential conversion efficiency well over 23% has been estimated

Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma

Background and Aims: Identification of prognostic factors for hepatocellular carcinoma (HCC) opens new perspectives for therapy. Circulating and cellular onco-miRNAs are noncod-ing RNAs which can control the expression of genes involved in oncogenesis through post-transcriptional mechanisms. These microRNAs (miRNAs) are considered novel prognostic and predictive factors in HCC. The apurinic/apyrimidinic endodeoxy-ribonuclease 1 (APE1) contributes to the quality control and processing of specific onco-miRNAs and is a negative prognostic factor in several tumors. The present work aims to: a) de-fine APE1 prognostic value in HCC; b) identify miRNAs regulated by APE1 and their relative target genes and c) study their prognostic value. Methods: We used The Cancer Genome At-las (commonly known as TCGA) data analysis to evaluate the expression of APE1 in HCC. To identify differentially-expressed miRNAs (DEmiRNAs) upon APE1 depletion through specific small interfering RNA, we used NGS and nanostring approaches in the JHH-6 HCC tumor cell line. Bioinformatics analyses were performed to identify signaling pathways involving APE1-regulated miRNAs. Microarray analysis was performed to identify miRNAs correlating with serum APE1 expression. Results: APE1 is considerably overexpressed in HCC tissues compared to normal liver, according to the TCGA-liver HCC (known as LIHC) dataset. Enrichment analyses showed that APE1-regulated miRNAs are implicated in signaling and meta- bolic pathways linked to cell proliferation, transformation, and angiogenesis, identifying Cyclin Dependent Kinase 6 and Lyso-somal Associated Membrane Protein 2 as targets. miR-33a-5p, miR-769, and miR-877 are related to lower overall survival in HCC patients. Through array profiling, we identified eight circulating DE-miRNAs associated with APE1 overexpression. A training phase identified positive association between sAPE1 and miR-3180-3p and miR-769. Conclusions: APE1 regulates specific miRNAs having prognostic value in HCC